TB control in risk groups DOTS-plus

1. TB control in risk groups DOTS-plus Lucica Ditiu, Antalya, April 2005

2. Risk of being exposed: no. of cases capable of transmitting M.tb, duration of infectiousness, no. and duration of encounters between a source and susceptible persons • Risk of becoming infected: no. of droplets produced by an infectious case, the volume of air, the “inhaling period “ • Risk of becoming sick after infected

3. Risk groups • Close contacts of persons known or suspected to have TB, infants and children esp. • Persons infected with HIV • Persons with medical factors known to increase the risk of progression from infection to disease: silicosis, gastroectomy, diabetes mellitus, chronic renal failure, jejunoileal by-pass, some hematological disorders (leukemia, lymphomas), other malignancies, treatment with high dose corticosteroid therapy and other immunosuppressive, weight 10% or more below ideal body. • Alcoholics and iv drug users • Residents of facilities such as: correctional institutions, prisons, mental institutions, nursing homes, long term facilities for elderly • Foreign born persons from countries with high TB prevalence, recently enterred a country • Health and other category of workers – in hospitals and other health care facilities, especially serving the high risk groups

4. These groups are now high priority, may decline in risk over time!!! • Responsibility of national public health officials to identify the risk groups using the national data

5. Risk of being exposed: no. of cases capable of transmitting M.tb, duration of infectiousness, no. and duration of encounters between a source and susceptible persons • Risk of becoming infected: no. of droplets produced by an infectious case, the volume of air, the “inhaling period “ IDENTIFY THE TB CASES AS QUICK AS POSSIBLE WHEN THEY PRESENT TO THE HEALTH CARE FACILITIES PLACE THE CASES ON EFFECTIVE TREATMENT, WITH THE REQUIRED FREQUENCY AND DURATION IMPROVE/INTRODUCE INFECTION CONTROL MEASURES IN SPECIAL SETTINGS – PRISONS, HOSPITALS, LABORATORIES

6. … will not prevent the new TB cases to appear from individuals infected long time ago!

7. Latent TB Infection (LTBI) • Identify LTBI – skin test (only for infection!) • Rule out active TB – clinical history, physical examination, chest X-ray, bacteriological exam. • Think about treatment of LTBI: can potentially reduce the risk of developing active TB versus hepatotoxicity, non-adherence, drug resistance (inefficient/creating), operational problems, cost.

8. Children under 5 years old – contacts with positive TB case (household) • INH 5 mg/kg for 6-12 mos • Persons infected with HIV and M.tb (annual risk of developing TB among HIV + is 6-16% in comparison with a lifetime risk of 10% for HIV-) • INH daily 9 mos • RMP + PZM daily 2 mos

9. TB and HIV • HIV is the most powerful factor known to increase the risk of TB • HIV increases susceptibility to M.tb and the risk of progression from infection to disease • Between 1% and 70% (sub-Saharan African countries) of TB patients are HIV +

10. HIV epidemic features in EUR • 75-85% of all HIV cases in Europe are male • 30-70% of all HIV cases are among younger than 25 years • Groups vulnerable to HIV: IDU, immigrants, ethnic minorities, prisoners, sex workers • Mainly IDU-related HIV transmission in Eastern Europe • Up to 30% of HIV infected females are IDU and 50% are partners of IDU • Similarities with the TB pattern: mostly males, younger in the East, older in the West, prisoners, immigrants

11. New TB cases notified by area; EUR, 1980-02 Russia 11th of the 22 TB high-burden countries

12. New HIV cases notified by area; EUR, 1995-03

13. Diagnosis and treatment: • Immunity only partial compromised – features are typical for TB • Clinical: less cough, less haemoptysis • Bacteriology: proportion of smear negative is greater; fewr organisms in sputum • Chest X-ray: normal – typical – atypical • TB drugs: Short course chemotherapy with RMP, given under DOT • No thioacetazone • Attention to SM! • ARVs: can determine development of active TB in a HIV+ LTBI or worsening the symptoms • Protease inhibitors and Non Nucleoside Reverse Transcriptase / RMP.

14. DRUG RESISTANT TUBERCULOSIS IS A MAN MADE PROBLEM! • RESISTANCE TO ANTI-TB DRUGS IS THE RESULT OF A CHROMOSOMAL MUTATION • DEVELOPMENT OF DRUG RESISTANCE IS THE RESULT OF INADEQUATE THERAPY – PHYSICIAN ERROR, LACK OF DRUGS, LACK OF ADHERENCE – (ADHERENCE TO SELF ADMINISTERED MEDICATION IS UNPREDICTABLE)

15. Drug Resistance Surveys • 3 Global Projects on DR (1997/35, 2001/58 and 2004/77 settings) New cases • 55.779 patients surveyed/75 settings • Prevalence of any resistance – 0-57% in Kazakhstan • Prevalence of MDR TB – 0–14.25% in Kazakhstan • Increasing trends in MDR TB : Tomsk Region and Poland • Increase due to: poor/worsening TB Control, immigration of patients from areas of high resistance, outbreaks of DR and variations in surveillance methodologies.

16. Drug Resistance Surveys Previously treated cases • 8,405 patients surveyed/66 settings • Highest prevalence of any resistance – 82.1% in Kazakhstan • Highest prevalence of MDR TB – 58.3% in Oman • Increasing trends for MDR TB : Estonia, Lithuania and Tomsk region.

18. Prevalence of MDR by treatment status, ranked by new cases

20. 5 components of DOTS - Plus • Sustained political commitment • Diagnosis of MDR-TB through quality-assured culture and drug susceptibility testing (DST). • Appropriate treatment strategies that utilize second line drugs under proper management conditions. • Uninterrupted supply of quality assured reserve antituberculosis drugs. • Recording and reporting system designed for DOTS-Plus programs.

21. Sustained political commitment • Long term investment in human and financial resources • Coordination efforts between community, local governments and international agencies • A well functioning DOTS program • Addressing the factors leading to the emergence of MDR-TB

22. Diagnosis of MDR-TB through quality-assured culture and DST • Proper triage of patients for DST and DOTS-Plus • Most programmes cannot do DST on all patient. Only patients with an increased risk for resistance are tested. • Some programmes will use strategies that target MDR-TB risk groups (failures, chronics). • In some settings with high prevalence of MDR-TB, DST may be done on all patients. • Relationship with SNRL

23. Appropriate treatment strategies that utilize second-line drugs under proper management conditions • Rational treatment design • Directly observed treatment • Monitoring and management of side effects • Human resources

24. Uninterrupted supply of quality assured second-line drugs • Many challenges for drug procurement • Regimens are frequently adjusted (side-effects, DST results, lack of treatment response) • Short shelf life (18 – 36 months) • Limited global production of quality-assured drugs • Drug registration may be a lengthy and costly

25. Recording and reporting system • Enables • patient registration • monitoring (including culture, DST, laboratory tests…etc) • interim indicators • final outcome analysis • comparison of different cohorts

26. Laboratory capacity: diagnosis and monitoring (culture, DST) Treatment design DOT during 18-24 months Management of (frequent) side-effects Often difficult patient categories Drug procurement and management DOTS-Plus recording & reporting system DOTS-Plus is far more complicated than DOTS

27. GLC-approved projects by March 2005 33 projects 11,000 patients GLC-approved DOTS-Plus projects Applications under review by the GLC Countries preparing application

28. Georgia – Abkhazia Latvia Kyrgyzstan Moldova Georgia Estonia Karakalpakstan, Uzbekistan Romania Russian Federation Arkhangelsk Orel Ivanovo Tomsk GLC-approved projects in EURO

29. Preliminary results of DOTS-Plus projects • More than 3000 patients have been enrolled and 1100 have completed treatment • MDR-TB among new cases in projects assessed range from 1.5-17.1% • 57% of the MDR-TB cases treated are resistant to all first line-drugs and also to second-line anti-TB drugs • All 5 first DOTS-Plus pilot projects assessed use individualised treatment regimens; average number of drugs used is 5 • Treatment success rates range from 61-82% • Only 2% of patients have stopped treatment due to adverse events

30. Preliminary resultsTreatment outcomes in some DOTS-Plus sites

31. Recent developments From pilot phase to expansion phase Mainstreaming DOTS-Plus (including DRS) into DOTS DOTS-Plus not longer limited to so-called "hot spots" Cat 4 regimens recognised as the standard of care for MDR-TB Politics: EB resolution 114.R1, GFATM DOTS-Plus guidelines are under revision SLD are used almost everywhere!

32. Conclusion • DOTS is priority to stop MDR-TB creation • DOTS-Plus should be built upon and fully integrated with DOTS – new vision of TB control • The GLC provides access to reduced-cost quality-assured second-line drugs and technical assistance • All GFATM financial support for MDR-TB must go through the GLC

33. DOTS-Plus is feasible under routine programme conditions • Country-specific: Frame-work approach! • Cost-effective intervention • Acceptable-good results, even in difficult patient categories • Mainstreaming DOTS and DOTS Plus is crucial in Eastern Europe

34. References • Global tuberculosis control: surveillance, planning, financing. WHO Report 2005. Geneva, World Health Organization WHO/HTM/TB/2005.349. • World Health Organization. Involving private practitioners in tuberculosis control: issues, interventions, and emerging policy framework. Geneva: World Health Organization, 2001: 1-81. • Hadley M, Maher D. Community involvement in tuberculosis control: lessons from other health care programmes. Int J Tuberc Lung Dis 2000;4(5):401-8. • World Health Organization. Guidelines for WHO Guidelines. Geneva: World Health Organization, 2003: 1-24. • WHO/IUATLD/KNCV. Revised international definitions in tuberculosis control. Int J Tuberc Lung Dis 2001;5(3):213-5. • World Health Organization. Toman's tuberculosis: case detection, treatment, and monitoring (second edition). Geneva: World Health Organization, 2004: 1-332. • World Health Organization. Treatment of tuberculosis. Guidelines for national programmes. Geneva: World Health Organization, 2003. • Enarson DA, Rieder HL, Arnadottir T, Trebucq A. Management of tuberculosis. A guide for low income countries. 5th edition. Paris: International Union Against Tuberculosis and Lung Disease, 2000. • Espinal M & T. Frieden What are the couses of drug-resistant TB? In Frieden TR, ed. Toman's tuberculosis. Case detection, treatment and monitoring, 2nd Edition. Geneva: World Health Organization, 2004: 207-208. • World Health Organization. Respiratory care in primary care services: a survey in 9 countries. Geneva: World Health Organization, 2004. • Harries A. How does the diagnosis of tuberculosis in persons infected with HIV differ from diagnosis in persons not infected? In:Frieden TR, ed. Toman's tuberculosis. Case detection, treatment and monitoring, 2nd Edition. Geneva: World Health Organization, 2004: 80-83. • Luelmo F. What is the role of sputum microscopy in patients attending health facilities? In: Frieden TR, ed. Toman's tuberculosis. Case detection, treatment and monitoring, 2nd Edition. Geneva: World Health Organization, 2004: 7-10. • Toman K. How many bacilli are present in a sputum specimen found positive by smear microscopy? In: Frieden TR, ed. Toman's tuberculosis. Case detection, treatment and monitoring, 2nd Edition. Geneva: World Health Organization, 2004: 11-13. • Toman K. How reliable is smear microscopy? In: Frieden TR, ed. Toman's tuberculosis. Case detection, treatment and monitoring, 2nd Edition. Geneva: World Health Organization, 2004: 14-22. • World Health Organization. TB/HIV: A clinical manual. Geneva: World Health Organization, 2004. • American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America. Treatment of tuberculosis. Am J Respir Crit Care Med 2003;167(4):603-62. • World Health Organization. Adherence to long-term therapies. Evidence for action. Geneva: World Health Organization, 2003. • Mitchison DA. How drug resistance emerges as a result of poor compliance during short course chemotherapy for tuberculosis. Int J Tuberc Lung Dis 1998;2(1):10-5. • World Health Organization. The Global Plan to Stop Tuberculosis. Geneva: World Health Organization, 2001. • Frieden TR. Can tuberculosis be controlled? Int J Epidemiol 2002;31(5):894-9. • Santha T. How can the progress of treatment be monitored? In: Frieden TR, ed. Toman's tuberculosis. Case detection, treatment and monitoring, 2nd Edition. Geneva: World Health Organization, 2004: 250-252. • Maher D, Raviglione MC. Why is a recording and reporting system needed, and what system is recommended? In: Frieden TR, ed. Toman's tuberculosis. Case detection, treatment and monitoring, 2nd Edition. Geneva: World Health Organization, 2004: 270-273. • UNAIDS/WHO. UNAIDS/WHO Policy Statement on HIV Testing: UNAIDS, 2004: 1-3. • Harries A. How does treatment of tuberculosis differ in persons infected with HIV? In: Frieden TR, ed. Toman's tuberculosis. Case detection, treatment and monitoring, 2nd Edition. Geneva: World Health Organization, 2004: 169-172. • Rieder HL. Contacts of tuberculosis patients in high-incidence countries. Int J Tuberc Lung Dis 2003;7(12 Suppl 3):S333-6.